The long term objective of the proposed research is to understand how the determination of cell fate is regulated in the developing olfactory epithelium. The two specific aims are: 1) To describe the patterns of cell proliferation in the developing olfactory neuroepithelium as they relate to the onset of odorant receptor expression, as a means to determine when olfactory receptor neurons are specified. 2) Examine if the timing of odorant receptor gene expression is regulated by cues from the embryonic environment or is a cell-autonomous process. These issues will be addressed in a vertebrate model system, the zebrafish Danio rerio. Elucidating the mechanisms of cell fate determination in the olfactory epithelium may shed light on the process of olfactory neuron generation that occurs in most vertebrates, including humans. More generally, these studies may provide more general insights into growth control and the maintenance of cellular identity, issues directly related to cancer. Cell proliferation and odorant receptor gene expression will be examined through a combination of cell labeling and in situ hybridization techniques. Transplantation of the developing olfactory epithelium between differently aged embryos will be used to determine if the embryonic environment produces molecular cues that induce or permit the expression the expression of specific odorant receptors. This technique will also determine whether the timing of odorant receptor expression is a cell-autonomous process. In addition, in vitro assays will be performed to screen for candidate molecules affecting the onset of odorant receptor gene expression in the na&iuml;ve olfactory epithelium.